There is at present growing interest in non-radioactively labelled modified oligodeoxynucleotides. Biotin (Agrawal et al. (1986) Nucl. Acids Res. 14:6227-6245; Agrawal (1989) Tet. Lett. 30:7025-7028), florophores (Cardullo et al. (1988) Proc. Natl. Acad. Sci. (USA) 85:8790-8794; Agrawal et al. (1988) J. Cell Biology 107:468; Haralambidis et al. (1989) Nucl. Acids Res. 18 (3) :501-505), intercalating (Helene et al. Oligodeoxynucleotides--Antisense Inhibitors of Gene Expression (Cohen, ed.) Macmillan Press (1989) pp.137-166) and chelating reagents (Oser et al. (1988) Nucl. Acids Res. 16:1181-1196) attached to synthetic oligonucleotides are becoming important tools of molecular biology. A variety of enzymatic and chemical procedures have been developed for their synthesis (Matthews et al. (1988) Anal. Biochem. 169:1-25). Central to some of these procedures are (a) the introduction of a reactive group at either the 3'- or 5'-terminus of the oligonucleotide (Agrawal et al. (1986) Nucl. Acids Res. 14:6227-6245; Agrawal (1989) Tet. Lett 30:7025-7028; Fidanza et al. (1989) J. Am. Chem. Soc. 111:9117-9119; Nelson (1989) Nucl. Acids Res. 17:7187-7194 or (b) the synthesis of modified nucleosides which contain the masked reactive group and are incorporated into the nucleic acid (Fidanza et al. (1989) J. Am. Chem. Soc. 111:9117-9119). The presently-available methods are useful, but are limited in their usefulness for site specific internal non-radioactive labelling of synthetic oligonucleotides.